Friday, February 29, 2008

BRAIN STIMULATION aims to be the premier journal for publication of original research in the field of neuromodulation. The journal includes: a) original articles (up to 5,000 words); b) brief reports (up to 2,000 words); c) invited and original reviews; d) technology and methodological perspectives (reviews of new devices, description of new methods, etc.); and e) letters to the Editor. Special issues of the journal will be considered based on scientific merit.

The scope of BRAIN STIMULATION extends across the entire field of brain stimulation, including noninvasive and invasive techniques and technologies that alter brain function through the use of electrical, magnetic, radiowave, or focally targeted pharmacologic stimulation. This includes investigations that study the effects of brain stimulation on basic processes, such as gene expression and other aspects of molecular biology, neurochemical regulation, functional brain activity, sensorimotor function, and cognitive and affective processes at the systems level.

The journal seeks the highest level of research on the biophysics and biopsychophysics of stimulation paradigms as well as the use of these techniques as a probe to outline patterns of neural connectivity. As an equal partner with this basic emphasis, the journal will have strong representation of research on the therapeutic potential and adverse effects of the stimulation technologies. The inclusion of research in therapeutics will represent not only clinical trials, but also conceptual pieces, discussions of ethics as they pertain to this field, services research, etc.

When reading her post I discovered that something was lacking. Besides the management of the treatment another important aspect is the coping with the depression. Some ordinary but useful measures can also help, such as running, light therapy, daily activity scheduling. May be she knows more examples than I can think of. Or anyone else some more suggestions?

Wednesday, February 27, 2008

About 40% of depressed adolescents do not respond to a Selective Serotonin Reuptake Inhibitor (SSRI). The combination of switching to a different antidepressant agent and receiving CBT resulted in a higher rate of clinical response than switching only to a different medication. There was no difference in response to the medication switches, and patients who were switched to a different SSRI experienced fewer adverse effects than patients taking venlafaxine.

This trial doesn't permit any conclusion to the shorter and more rational strategy of adding cognitive behavioral therapy to the first antidepressant with lack of response. The strategy researched in this trial has a disadvantage of first switching to another antidepressant (SSRI of venlafaxine) together with CBT. This will at least take a couple of weeks.

DesignIn this trial adolescents with depression who had not responded to an initial 2-month treatment with an SSRI and had not received cognitive behavioral therapy (CBT) were randomly assigned to switch for 12 weeks to 1 of the following treatment strategies: (1) a second, different SSRI, (2) a different SSRI and CBT, (3) venlafaxine (a selective serotonin and noradrenergic reuptake inhibitor), or (4) venlafaxine and CBT.

They did not control for the greater contact and attention that participants in the combined treatment received (eg, by offering supportive therapy in the non-CBT groups. However, prior to entry, these participants had not responded to a fairly intense regimen of treatment, consisting of a median of 17 weeks of pharmacotherapy and 8 sessions of psychotherapy over the previous 12 weeks. Also, 2 characteristics of this sample, namely high rates of chronicity and clinically significant suicidality, have previously been shown to predict a poor response to supportive therapy in adolescents with depression.Second, the blinding with regard to CBT was compromised in about one-fifth of the sample, but since the effects of CBT persisted even after statistically controlling for the effect of unblinding, the compromise in the blinding alone does not explain our findings. Third, due to our design, we cannot determine whether the addition of CBT would have been beneficial even without making a change in medication.

Brent, D. (2008). Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral Therapy for Adolescents With SSRI-Resistant Depression. The Journal of the American Medical Association, 299(8), 901-913.

Tuesday, February 26, 2008

Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients.

This is the conclusion of a meta-analysis of all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. These antidepressants are: include fluoxetine, venlafaxine, nefazodone, paroxetine. The article is published in PloS Medicine and free to read. They specifically tested the influence of depression severity and outcome of these newer antidepressants compared to placebo.

The overall result of the meta-analysis comparing these new antidepressants with placebo confirmed earlier analyzes. Weighted mean improvement was 9.60 points on the HRSD in the drug groups and 7.80 in the placebo groups, yielding a mean drug–placebo difference of 1.80 on HRSD improvement scores. Although the difference between these means easily attained statistical significance it does not meet the three-point drug–placebo criterion for clinical significance used by NICE.

They also found that efficacy reaches clinical significance only in trials involving the most extremely depressed patients, and that this pattern is due to a decrease in the response to placebo rather than an increase in the response to medication.

Now I am not a great fan of these newer antidepressants especially with severe depression. In the past Anderson and others have shown a couple of times in reviews and randomized controlled trials that TCA are significantly better for depressed inpatients. These inpatients with depression are more likely to be suicidal, psychotically depressed (30%) and suffer from psychiatric and somatic co morbidity. In the review by Anderson the Tricyclic Antidepressants were used in a low average dosage and mostly not plasma controlled. Patients can benefit from plasma level controlled dosing of tricyclic antidepressants. Therapeutic dosage is reached faster, and side-effects due to a high dosage is prevented.

This outcome of this meta-analysis seems to bold to be true, might be the selection of trials?

Monday, February 25, 2008

This is the title of a recent article in British Medical Journal. It is accurate, precise, and important information not only for professionals but it could also benefit patients. It is not yet free online, you will have to wait another 12 months.

Nevertheless the two most important conclusions to my opinion are about the components of a comprehensive management plan and factors associated with increased risk for recurrence of depression. These are important because this knowledge make patients better prepared and equipped to judge about there own treatment and to discuss different options with their psychiatrists or primary physicians.

Components of a comprehensive management plan for depression. Adapted from American Psychiatric Association and World Federation of Societies of Biological Psychiatry guidelines

Determine the pharmacological or psychosocial treatment

Determine the treatment setting

Establish and maintain a therapeutic alliance

Monitor and reassess the patient’s psychiatric status in the course of treatment

Monitor the patient’s response to treatment

Reassess the adequacy of diagnosis when appropriate

Monitor possible side effects and physical condition

Enhance treatment adherence

Educate patients and their families about the nature of the illness (psychoeducation)

Now these are all important considerations to make by a psychiatrist or primary physician. This is not always shared with their patients but could be important topics to discuss. So go over them slowly and look for yourself if any of these components leaves you with questions regarding your own treatment and discuss it with your doctor.

Factors associated with increased risk for depression recurrence. Adapted from World Federation of Societies of Biological Psychiatry guideline

Now these are all very important risk factors. Continuation therapy is not a go or nogo decisions. It is a balance between several options which might take a while and a lot of discussion before a treatment for the long term is agreed upon by patient and doctor.Timonen, M., Liukkonen, T. (2008). Management of depression in adults. BMJ, 336(7641), 435-439. DOI: 10.1136/bmj.39478.609097.BE

Posted a while ago about this game vest, it is now on the market for only 169 dollars. I am still waiting for FDA approval for the medical version. The medical version of the vest is more sophisticated, enabling doctors sitting at their computers to prod, poke and press patients' bodies from afar and get feedback on what they are virtually feeling.

The FPS Vest ($169) lets you take your first-person shooter experience to the next level with eight active zones that simulate the direction and forces of bullet fire, crushing explosions, and finger taps as they occur in the game. It comes with two PC games designed to show off the vest, letting you jump right into the action.

Nothing about depression or ECT. This weekend I went away for the weekend, to Maastricht the capital of Limburg, one of our "states" (regions or county's, don't know what I should call them). Besides hiking a lot of shopping as well as dining. Loved it so her are some pictures. And a map so you know were it is.

Saturday, February 23, 2008

The D:Scribe is a pen that digitizes your writing to send as a text message. You write whatever you want, circle the name of the recipient, and the pen sends the data to your cell phone via Bluetooth, which in turn fires off the text or email message. The current status of messages is displayed on the pen's little OLED display.

This post at geekology about a special digital pen got my attention. I love pens especially fountain pen. Since PC's and electronic patient files a pen is hardly used anymore. I used to have a whole range of fountain pens. Since a couple of years I am the proud owner of a Montblanc fountain pen. It was a present for my birthday from my colleagues. I sometimes look for excuses to use it. May be they should invent a fountain pen for blogging.

A pen that can record what you are writing as well as record and sync audio with whatever you write, so you never miss a word. With Paper Replay, users can tap on their notes written on paper to hear exactly what was said. They can also fast forward, rewind, jump ahead, pause, and even speed up or slow down their audio recordings using controls printed on the bottom of each page. Yes your notes on the computer screen as well as on paper. You will have to see it to believe it Have a look at the demo video's at livescribe.comYou can't buy it yet, takes a couple of months.

You can use the Mobile Notetaker everywhere without a computer. The device stores everything you write in its internal memory. When you are back at home/your office - simply upload it to your computer. The internal flash memory can store up to 50 pages (size A4). The Mobile Notetaker is powered by 2 AAA Batteries and has a unique LCD screen to confirm input.

Friday, February 22, 2008

Google Inc. will begin storing the medical records of a few thousand people as it tests a long-awaited health service that's likely to raise more concerns about the volume of sensitive information entrusted to the Internet search leader. The pilot project announced Thursday will involve 1,500 to 10,000 patients at the Cleveland Clinic who volunteered to an electronic transfer of their personal health records so they can be retrieved through Google's new service, which won't be open to the general public.

Thursday, February 21, 2008

The short history of Vagus Nerve Stimulation (VNS) in treatment resistant depression is hampered by some drawbacks. Scientifically the results of a double-blind randomized sham controlled trial with no definitive evidence of short-term efficacy for adjunctive VNS in treatment resistant depression were of major importance.

Of human interest was the undisclosed background of Dr Nemeroff, then editor in chief of the journal in which he published a review about VNS for treatment resistant depression. Not only did he not disclose his position as head of the "mechanism of action" advisory board at Cyberonics; the paper's first draft was written by a ghostwriter hired by Cyberonics. You can read more about the Nemeroff Saga at Clinical Psychology and Psychiatry. Cyberonics is the firm making these devices.

VNS is:

VNS therapy includes surgical implantation of a small battery-operated pulse generator - similar to a pacemaker - in a patient’s left upper chest. Thin, flexible wires from the device are tunneled into the neck and send mild, intermittent pulses to the neck’s left vagus nerve. The vagus nerve in turn delivers these pulses about every five minutes to the areas of the brain involved in the regulation of mood, motivation, sleep, appetite and other symptoms relevant to depression.

A 12 month naturalistic follow-up study after the acute phase trial with VNS used as an adjunct to other antidepressant treatments in patients with treatment resistant depressions revealed a statistic significant decrease of 0.45 points/month on the 24 item version of the Hamilton Depression Rating Scale.Response defined as a 50% or more reduction of HRSD score was achieved by 27.2% of patients (55/202), remission defined as a final score of 10 or less was present in 15.8% of patients (32/202) after 12 months (LOCF). Both the VNS and the other antidepressant treatments could be adjusted during this 12 month follow-up.

A third study in the same issue of the journal Biological Psychiatry tried to add a non-randomized control group to the first two studies mentioned above (acute phase trial and the 12 month follow-up). This control group was not intended to serve as a control group but was originally intended to serve as a group for comparison of health care costs. Besides switching the purpose of a control group the study was not randomized nor blinded. The use of only the secondary positive outcome from the first trial makes the results of this trial in favor of VNS with treatment as usual compared to treatment as usual questionable.

The authors mention the argument sometimes used that it is unethical to use a controlled design with a sham condition. We are talking about patients treated with 3-7 different antidepressants and/or ECT. Mostly ill for years. I think it unethical to conduct another uncontrolled trial which will help our knowledge about the efficacy of VNS no further. Besides implanting a VNS is not peanuts nor going to a protocol of up to 1 year.

Anyway, this open study also finds that the efficacy of VNS increases over time. The follow-up in this study is up to 12 months. Again efficacy is hard to interpret since it open labeled uncontrolled design. A more positive view on the data of this trial can be found on the blog of the first author: VNS on Therapeutic Neuromodulation

It is hard to make a final conclusion on the clinical relevance of these outcome data. The response and remission are not impressive, nevertheless the patients in these trials are usually depressed for a long time and they have been treated with several antidepressants including ECT.

The question remains whether these benefits of VNS can be attributed to VNS or the natural course of depression or other possible confounders such as the concurrent treatment during the trials. At least VNS could be well tolerated by the participants and these trial suggests a potential long-term growing benefit of VNS in treatment resistant depression. The clinical relevance of this growing benefit needs to be established. Something worth while examining in the future in a double blind fashion.

Wednesday, February 20, 2008

During your residency in psychiatry in The Netherlands you have to have at least 50 sessions of psychotherapy. This is done for several reasons.

The first one is of course the notion that in performing psychotherapy, the relationship is the very instrument of the treatment. Residents in psychiatry should be aware of their own feelings about their patients — a process called countertransference.

Another advantage is the awareness of what it means to be in psychotherapy for a patient. And sometimes residents can benefit from the treatment of their own complaints. Sometimes this therapy is useful for their own complaints and can be followed by further psychotherapy.

But even as we have been swept off our feet by sexy neuroscience, my field is in danger of losing touch with the rich psychological life of patients, something that is reflected in the waning popularity of therapy during residency training.

And this one

We can effectively relieve symptoms and increase functioning, but we still have to help our patients live with illness.

Tuesday, February 19, 2008

9 Curricula were identified in a literature search for curricula addressing resident-pharmaceutical industry relationship. Lack of experience may make young doctors particular vulnerable to pharmaceutical industry influence. These interactions between doctor and pharmaceutical companies have an impact on doctor knowledge and prescribing practice. The pharmaceutical companies have different and efficient marketing techniques to influence doctors. Residents may be even more influenced when not educated about these threats.

Inconsistency in content (of the curricula), application and evaluation methodology prevents any meaningful synthesis of data

This was the conclusion of a systematic review of the curricula.

The literature search obtained 121 articles, of which 78 did not address relationships between doctors and the pharmaceutical industry. 10 were selected for detailed review. Only 9 could be used and only 8 included an evaluation component of which only 1 included a control group. Only 2 evaluations used a validated outcome instrument, and no studies included longterm follow-up. Modest improvement were noted in residence confidence, knowledge of guidelines.

A lot remains to be done. More curricula with better education are needed. Standardization of evaluation for establishing change in attitude and behaviors are also needed.

Monday, February 18, 2008

Professional writers spend most days of their adult lives writing. For those among them who specialize on long form non-fiction, their writing is not that different from the types of research papers that plague college students. Assuming that these writers do not want to spend most of the days of their adult lives hating what they are doing, it stands to reason that, over time, they have figured the least painful possible way to schedule a large amount of writing.

The most important rules are:

get up in time, between 7 and 8 am

work for 2 to 3 hours than stop for a short break

work in isolation, don't get distracted by phone or e-mail

from the comments

If you sit down at your specified time and are drawing a blank, get a new document/piece of paper and freewrite. Write ANYTHING, even if you just write “I have no idea what to say” over and over. Ignore spelling and grammer. Write stream of consciousness. Just get something on the page. Eventually something will click and you will start to come up with ideas that are more useful.

We're beginning to finalize our program for Games for Health 2008 on May 8-9 in Baltimore.

We're planning close to 40 sessions including sessions on epidemiology in World of Warcraft, Game Addicition, Nurse Training, Rehabitainment, and a special session with some of the biggest companies in healthcare.

Stay tuned there is much more to come but click through to see some of the great content planned thus far for our largest event yet!

This is the announcement for the new conference. A lot of interesting subjects will be presented in sessions about (computer) games in health care.

For example:

The Case of the Food Detective Game

In this session Kaiser Permanente presents a case study of its Amazing Food Detective Game (www.kp.org/amazingfooddetective). The game, aimed at children ages 9-10 and available to everyone at www.kp.org/amazingfooddetective, complements Kaiser Permanente's nationally recognized childhood obesity clinical strategy. Based on a popular character from Kaiser Permanente's Educational Theatre Program, the Amazing Food Detective takes children through activities that show how to choose healthy foods and get more active. Children playing the game follow the routines of eight culturally diverse children whose activities or conditions would benefit from healthy food and exercise choices.

Ever wondered what exergaming was? So did I. Well go and see for yourself

The History of ExergamingWhile exergaming is widely considered a recent emerging game genre it actually is a style of videogame that has existed for quite some time. Exergaming in fact has a close to 30 year history of development activity. In this well researched session attendees will be exposed to a deep history of exergaming products that offers some important insights into one of the most successful areas of the games for health field.

Sunday, February 17, 2008

I think the latter. Heard this number this afternoon on the radio, couldn't get it out of my head, terrific. In the record you can also hear a Spanish Speaking Woman. This is live.No mp3 available, search the whole @#!!% Internet.Enjoy!

Future search will depend heavily on what the engine knows about you: Where you live, what your friends like, and what you’ve found useful in the past. It’s unlikely that the average consumer will invest time and effort in building redundant online personas across several search engines in order to improve results.

Users make very little use of advanced search facilities, they assume that search engines understand their query's. Many new search sites are trying to build a better mousetrap by trying new appraoches. You can read about the reasons why the World Needs Another Way to Search?

All in all, Yahoo and MSN seemed to have the most interesting changes among countries. Please note that we didn’t take screenshots from all of the countries out there. We just tried to find the more interesting pages out there that had something different compared to others. For the best viewing experience, click on each image to enlarge it. Once you click on one image, just use your arrow keys to flip through all of the images.

Friday, February 15, 2008

What follows are citations for some of the larger published studies looking at VNS. Patients and psychiatrists will often be involved in applying for funding for further assessment/ treatment, and it is helpful to be able to state what the evidence is. All of these papers should either be available through the NHS e-library, or through any NHS/ hospital library.

ScientificMatch uses your DNA to maximize the chances of finding chemistry—actual, physical chemistry—with your matches. We look at your personal values to help you find a soul mate. And our in-depth background checks provide one of the safest—and most honest—places for your search.

We faithfully guard your DNA. Your genetic information is never made public—not even you can see it. Our lab never knows whose DNA they’re looking at. We only analyze a very few of your immune system genes—not your whole genetic makeup. And your DNA sample is destroyed after we’re done with it. With all our safeguards, your genetic privacy is more vulnerable when you get a hair cut and leave the trimmings on the floor!

Thursday, February 14, 2008

Even a Dutch research group published a placebo controlled trial with rTMS. Not that they found rTMS to be significantly better than sham TMS after two weeks of treatment. Both groups had a reduction of 2.5 points on the Hamilton Depression Rating Scale (17-item version) and 1 point in the second week, the decrease never passed 20% in either group.

Their point being a continuing improvement in the rTMS and the sham rTMS group during the follow-up of 3 months. This resulted in a significant mean difference of more than 4 points in favor of the rTMS group over the sham group. Now that is weird, stopping a treatment and patients continue to improve in both groups, favoring the real treatment group.

This could be explained by some shortcomings of this trial:

The placebo condition was treatment with the coil in an angle of 45 degrees, it is argued that this is not really a sham condition but could still have an effect.

The dosage was set at 80% of the motor treshhold which is low, mostly a dosage of 120% is used.

Groups differed in their male/female ratio

Early drop outs during treatment were not included in the analysis.

Patients were kept on medication such as benzodiazepines and antidepressants.

Localisation of rTMS

With rTMS the location were the treatment is applied is usually on the Left Dorsolateral Prefrontal Cortex (LDPC). This localization is based on localizing the part of the left motor cortex representing the muscles of the right thumb (abductor of the pollicis brevis). Stimulation leads to a twitching of the right thumb. The coil is placed about 5 cm in front of this mark. Mostly a frequency of 1 or more HZ is used, stimulation of 1 or more per second. This results in activation of neuronal tissue.

In a recent publication the they tried low frequency over the right cortex. They placed the coil 5 cm in front of the right motor cortex. Low frequency reduces neuronal firing of the cortex. The treatment group showed significant improvement, the sham group didn't. Improvement meaning a reduction on the Hamilton Rating Scale for Depression. Group comparison was not performed, probably because this wouldn't result in a significant difference because the groups were very small (6 patients each). All patients having benefit from treatment relapsed within 2-3 months.Limitations besides small sample size: placebo condition was again applying the coil in 45 degrees which might not be placebo after all, patients received antidepressants and benzodiazepines during the trial.

The application of left or right TMS was also studied in a larger sample of treatment resistant depressed patients who continued their antidepressants and anticonvulsants during the trial. High frequency left-sided repetitive TMS was compared to low frequency stimulation to the right prefrontal cortex. Both conditions were better than sham condition although their efficacy was not impressive after 2 weeks. Even a further single blind continuation didn't result in clinical impressive efficacy. What this research learns us is that maybe we should increase the number of treatments and the number of stimuli. Until now mostly 10 days during 2 weeks with 10000 stimuli might be to less. Maybe non response to left high frequency might be followed by right low frequency as treatment option. Limitations were blindness of patients,and continuation of medication during treatment.

Response prediction

A brave attempt was made to look at response prediction for rTMS. Number of antidepressant trials before treatment and current illness duration were a priori hypothesized as of importance for response to rTMS. In this placebo controlled trial with 15 subjects (7 rTMS, 8 sham rTMS) no significant advantage for active rTMS over sham rTMS could be shown as a treatment for depression. Nevertheless the authors suggests that short ilness duration (less than 4 years) predicts better improvement compared to the group with an illness duration of 10 or more years. Subjects with 7 or more antidepressant trials (lifetime) did better than those with fewer trials.Limitations of this trial:small sample size, inadequate placebo condition, recruitment of patients with advertising, selected patient sample relatively young,and long illness duration.

ConclusionsTogether with a prior post as update number 1 on rTMS it can be concluded that efficacy of rTMS in depression is not impressive if any. Many questions still remain to be solved before it can be added to the arsenal as treatment for depression. The most important questions are:

Which technical decisions should be made about frequency of treatment, duration of treatment, localization of treatment (left or right)

Which patient group might benefit: treatment resistant patients or not treatment resistant patients.

Wednesday, February 13, 2008

High-dose Magnetic Seizure Therapy on rhesus monkeys results in benign acute cognitive side-effect profile relative to Electroconvuslive therapy. This is in line with earlier reports. This time a more powerful MST device was used.

In randomized order, subjects received 20 days of ECT, high-dose MST, and sham treatment (anesthesia alone). A recovery phase, with a minimum of 20 days and a maximum of 30 days, immediately followed each treatment phase. The length of the recovery period was determined by a return to baseline performance.

The monkeys were trained on five cognitive tasks assessing automatic memory, anterograde learning and memory, combined anterograde and retrograde simultaneous chaining, and spatial and serial working memory. Acutely after each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-hour retention interval.

This research showed that chronic treatment with high-dose MST resulted in less cognitive impairment than ECT and that high-dose MST did not significantly differ from the effects of anesthesia alone.

These results support the feasibility and safety of high-dose MST for subsequent work in humans to assess its efficacy in the treatment of depression.

Limitations of the study:

the small sample size

the limited number of cognitive domains assessed

the risk of carry-over effects

practice effects

all three monkeys were males

Advantages of MST

Magnetic seizure therapy (MST) is under development as an alternative convulsive technique to minimize the neurocognitive adverse effects of convulsive therapy while maintaining antidepressant efficacy. Preclinical testing suggests that MST might have several advantages over ECT, including increased precision of stimulation, greater control of intracerebral spatial distribution, lack of susceptibility to impedance from surface tissues, and the sparing of deep brain structures

Monday, February 11, 2008

Patients who are younger and depressed and have made a suicide attempt within a month prior to a media report of a celebrity suicide are at increased risk of a subsequent suicide attempt. The increase was almost 12 times higher than subjects with no previous attempt, 8 times higher to those with a suicide attempt within a half year, and further to 2 to 3-fold among those with a suicide attempt of longer than a half year.

Factors influencing the risk of media influences

Age under 55 years

Previous suicidal behavior

Presence of depression

438 Depressive patients from psychiatric outpatient clinics of 6 medical centers in Taiwan were interviewed by psychiatrists. They were interviewed for suicide attempts or suicidal thoughts, psychiatric diagnosis and the clinical status of the patients depression before the first media report was assessed.

About one third of the respondents said that the reporting had a negative influence on their subsequent suicidal thoughts and attempts. In 5.5% there was a suicide attempt.The media influence reached it's peak at 40 days.

Medblog English has updated his Medblog list. I am on number 32 due to the fact that he has divided the list in categories.

I have upgraded the MedBlogEN-list. Firstly I categorized the medblogs. I tried to find what the writers’ profession was. I made a distinction between physicians, pharma-people, nurses, patients, paramedics, journalists, managers, others and unknows. It is ofcourse possible that I made mistakes. So please let me know if I wrongly categorized a medblog. Secondly I removed non-relevant or closed sites from the list. The list is now pretty up-to-date. If you want to add your medblog to the list, please send an e-mail to jan @ medblog.nl. Don’t forget to mention your profession in the mail. And please include the url to your feed.

Sunday, February 10, 2008

Depression and burnout are major problems among residents in paediatrics. Depressed residents made significantly more medical errors than their non-depressed peers; however, burnout did not seem to correlate with an increased rate of medical errors.

The information in this review suggests that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit.

Considering the outcome on the time point at week 4, Dr Shock is not very impressed by the results. For significant difference with the primary outcome 6 patients had to be excluded from the analysis. The mean difference between active and sham on the severity scales is in the range of 2-3 points, significant but hardly clinical relevant. Absolute figures on response and remission at week 4 are not given in this article. Remission rate at 6 weeks on the HAMD-17 was 15.5% increasing to 22.6% at week 9 with open labeled therapy. Not very impressive.

This same group studied rTMS as form of long-term maintenance therapy for depression. 10 Patients who had responded to an acute course of rTMS for their depression participated in this open label case series. The maintenance rTMS ranged from 6 months to 6 years for these patients.The maintenance rTMS was started directly after response to the acute treatment. Response was defined as a reduction of 50% or more on the 17-item Hamilton Rating Scale for Depression.

rTMS was applied to the left prefrontal cortex at 100% of motor threshold. This location is mostly used in depression. The dosage seems low, usually 120% or 130% above motor threshold is used. The number of pulses per session ranged from 2000-3000. The frequency of sessions was determined by the clinical course of the patient.

5 Patients experienced marked benefit of maintenance rTMS (a mean of 257 sessions) with a mean of 2.1 sessions per week. Three of them didn't need additional treatment such as antidepressants.

2 Patients experienced moderate benefit of maintenance rTMS. Both experienced a recurrence of a depressive episode in a period of 12-18 months. They received a mean of 125 sessions with a frequency of 1.8 per week.

3 Patients received no benefit of maintenance rTMS.

Two patients were still treated with rTMS as maintenance treatment at the time of publication (2005). No serious side effects were reported.

LimitationsOpen label, no fixed treatment parameters, small number of patients.

In another study augmentation of amitriptyline with rTMS was studied. 46 Outpatients with non-psychotic depression were randomized to rTMS or sham rTMS (using a placebo coil). During 4 weeks with 5 sessions of stimulation over the dorsolateral prefrontal cortex, 5Hz rTMS, 120% above motor threshold. The subjects received 1250 pulses per day. Seven days prior to the start of rTMS all patients received 50 mg of amitriptyline at evening and the dose was increased by 50 mg every second day. The mean daily dose was 110.2 mg/day which is considered to be very low.

The response rate and remission rates were significantly higher for rTMS compared to sham rTMS, response was 95% versus 46%, which is unusually high. Remission was 54% versus 12%. Real rTMS showed a significant difference with sham rTMS at the end of the first week of this four week trial. These results are in contrast with 3 earlier add-on studies. Two trials with a sham controlled design couldn't find a significant difference between real rTMS and sham rTMS as add-on strategy. The other trial was an open label trial.

This result is also in strong contrast with a recent add-on study of rTMS to mirtazepine and venlafaxine. This augmentation study is discussed in a recent post on this blog: rTMS augmentation not useful.

Repetitive Transcranial Magnetic Stimulation (rTMS) together with mirtazapine or venlafaxine was not better than these antidepressants with sham rTMS. Response in both treatment groups was 31%, response defined as a reduction of 50% or more on two of three depression severity scales. Even the decrease of scores on the depression rating scales did not differ significantly between real and sham rTMS.There was also no accelerated antidepressant effect, no acceleration of a clinical improvement.

Saturday, February 9, 2008

St. Jude Medical Inc. (STJ) has garnered Food and Drug Administration approval to launch a trial the company plans to use to pursue U.S. approval for a pacemaker-like device that uses electricity to treat severe depression.

Friday, February 8, 2008

So far I have found three guidelines about ECT with adolescents for depression. Summarized these guidelines suggest the following recommendations:

ECT is not recommended for children (5–11 years).

ECT should only be considered for young people with very severe depression and either life-threatening symptoms (such as suicidalbehaviour) or intractable and severe symptoms that have not responded to other treatments.

ECT should be used extremely rarely in young people and only after careful assessment by a practitioner experienced in its use and only in a specialist environment

This is roughly the conclusion after reading these three guidelines. This conservative opinion is based on the lack of controlled studies. Most publications on adolescents are reviews of single case studies or case series using variable methodology and variable outcome measures. This makes a positive publication possible, only positive outcomes are published.

Side effects are also not studied in controlled trials but only small retrospective case series and case reports. It seems that adolescents appear to have the same side effects as adults. There are no studies which provide evidence of the impact of ECT in developing brain.

Parents are generally as positive, or more positive in their views on ECT than adolescents who had received the treatment.

The above mentioned recommendations mainly come from the guideline of the National Institute of Clinical Excellence (NICE): Depression in children and young peopleDepression in children and young people: identification and management in primary, community and secondary care. Compared to the Practice parameters for the assessment and treatment of children and adolescents with depressive disorders of the American Academy of Child and Adolescent Psychiatry (AACAP)the NICE guideline is more comprehensive. In the AACAP guideline ECT is only mentioned for psychotic depression.

In adults, electroconvulsive therapy (ECT) is particularly effective for this subtype of depression. Non-controlled reports suggest that this treatment also may be useful for depressed psychotic adolescents.

Diagnosis: Severe, persistent major depression or mania with or without psychotic features; schizoaffective disorder; or, less often, schizophrenia. ECT may also be used to treat catatonia and neuroleptic malignant syndrome.

Severity of Symptoms: The patient's symptoms must be severe, persistent, and significantly disabling. They may include life-threatening symptoms such as the refusal to eat or drink, severe suicidality, uncontrollable mania, or florid psychosis.

Lack of Treatment Response: Failure to respond to at least two adequate trials of appropriate psychopharmacological agents accompanied by other appropriate treatment modalities. Both duration and dosage determine the adequacy of medication trials. It may be necessary to conduct these trials in a hospital setting.

ECT may be considered earlier in cases in which

adequate medication trials are not possible because of the patient's inability to tolerate psychopharmacological treatment;

the adolescent is grossly incapacitated and thus cannot take medication;

or waiting for a response to a psychopharmacological treatment may endanger the life of the adolescent.

I can live with the above mentioned first three points. I would like to develop two or three Dutch ECT centers especially for treatment of adolescents with extensive research protocols.

Thursday, February 7, 2008

We have an elderly patient admitted to our ward for second opinion. She has a history of depressive episodes. Two post partum depressions and one depressive episode about 6 years ago. She is 72 years old.

When I met her the first day she was in a dysphoric mood complaining about her transfer to our department. She already took nortryptiline for 2 months with adequate plasma levels. Her referring psychiatrist said that this had led to some improvement, the patient was less pleased with the antidepressant. According to her this drug was causing memory problems.

She demanded ECT since that was the reason for her transfer.

During the observation period she had depressive symptoms as well as cognitive symptoms.

Dementia and depression are frequently comorbid among older adult patients.Depression is related to cognitivedecrement and can even represent the first signs of a neurodegenerative process.It can be difficult to distinguishdepressed patients exhibiting the first signs of dementia from those whose cognition will improve with treatment.

How can we differentiate between depression and dementia?

Neuropsychological assessment is generally considered the gold standard in differentiating between depression and the early stages of dementia.

Cognitive impairments in dementia are usually more severe than in patients with depression.

Patients with depression will do more poorly on tasks that require more effort to complete a task. Patients with dementia score low on tests because of ability-based deficits rather than on the amount of effort needed for the test.

Patients with depression generally retain the learned information during testing, patients with dementia show a higher rate of forgetting of initially recalled material over time. Besides these retrieval deficits in patients with dementia, memory consolidation is also worse compared to depressed patients as shown with recognition memory tasks.

Patients with beginning dementia exhibit greater false-positive scores whereas depressed patients usually stay on the save side and produce more false negative errors. Patients with dementia show specific impairments such as practical shortcomings, difficulty with temporal relationships between events.

It is not clear which depressed elderly is predisposed to develop dementia from those depressed elderly that will not. It is suggested from the literature on this subject that depressed patients exhibiting early decrements on tasks of recall memory, visuospatial skills (Visuospatial skills allow us to visually perceive objects and the spatial relationships among objects.), and executive functions may be at greater risk for developing dementia than patients without such a degree of decrement.

The depression symptoms that might predict development of dementia are:

Apathy during a depressive episode, which is disinterest, low energy, and concentration difficulties is a risk factor for developing dementia later on as shown by a 3-year longitudinal study.

Apathy is also positively associated with dementia severity, dysphoria has a negative relationship.

Fewer affective symptoms such as feelings of guild, depressed mood, suicidal ideation, and more agitation and motor slowing are positively associated with dementia.

Late onset depression, that is a first depressive episode at a later age, is a risk factor for dementia than for early onset depressive disorder.

The presence of white matter and subcortical gray matter hyperintensities in imaging studies are positively related with depression during old age. The boundary between vascular dementia and Alzheimer dementia is less clear than once hypothesized. Patients with hypertension have increased amounts of senile plaques and neurofibrilllary tangles and previous high cholesterol is positively associated with Alzheimer disease. At least a part of the relationship between geriatric depression and dementia can be explained by a vascular compromise to the frontostriatal circuit.

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is represented by high levels of glucocorticoids during depression. In depressed patients with hypercortisolemia cognitive deficits have been demonstrated together with lowerded hippocampal formation volume and reduced metabolism. There is a possibilty that hippocampal atrophy associated with HPA dysfunction in depression might be a risk factor for developing dementia later on.

Depression as a prodrome of dementia. In a subset of older adults depression can represent the first symptoms of dementia even when accounting for cognitive complaints. It is unknown whether vascular compromise of the frontostriatal regions, structural damage by cortisol dysregulation or both account for this relationship.

Depression as a risk factor for dementia. Due to lack of good prospective longitudinal studies this relationship remains to be seen.

Where does this leave our elderly patient?Her dysphoric mood and prior history of depressive episodes (no late onset) makes me more optimistic about her cognitive symptoms. Neuropsychological testing is our first goal although her depression might be to severe for a reasonable test outcome.I'll keep you posted.

About Me

Dr Shock is a pseudonym for a psychiatrist working in a University Hospital. His main topics of interest are the treatment of depression and electro convulsive therapy. Other subjects for this personal blog are research, article reviews, book reviews and education. He loves computers and Internet.